Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury

Sharon Andreoli, Coleen Mallett, Kathy Williams, James A. McAteer, Robert Rothlein, Claire M. Doerschuk

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10-7 FMLP/cylochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 ± 1.0 to 92.5 ± 7.0% of the activated PMNs were adherent to mesothelial cells compared to 6 ± 1.8 to 27 ± 2.4% of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41% of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B. Immunohistochemical studies demonstrated that the cultured mesothelial cells express intracellular adhesion molecule 1 (ICAM-1) and FAB fragments of a monoclonal anti-ICAM-1 antibody partially reduced adhesion of activated PMNs to mesothelial cells and slightly reduced mesothelial cell injury. Staphylococcus aureus, Staphylococcus epidermidis, alpha streptococci, and Pseudomonas aeruginosa at concentrations of 103 to 105 bacteria/ml caused little to no ATP depletion or 51chromium release. We conclude that activated PMNs adhere to human mesothelial cells and induce mesothelial cell injury; such injury can be,partially reduced by blocking adhesion of activated PMNS to mesothelial cells.

Original languageEnglish
Pages (from-to)1100-1109
Number of pages10
JournalKidney International
Volume46
Issue number4
StatePublished - Oct 1994

Fingerprint

Neutrophils
Wounds and Injuries
Adenosine Triphosphate
Cell Line
Cytochalasin B
Staphylococcus epidermidis
Tetradecanoylphorbol Acetate
Streptococcus
Pseudomonas aeruginosa
Staphylococcus aureus
Cultured Cells
Monoclonal Antibodies
Bacteria
Antibodies

ASJC Scopus subject areas

  • Nephrology

Cite this

Andreoli, S., Mallett, C., Williams, K., McAteer, J. A., Rothlein, R., & Doerschuk, C. M. (1994). Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney International, 46(4), 1100-1109.

Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. / Andreoli, Sharon; Mallett, Coleen; Williams, Kathy; McAteer, James A.; Rothlein, Robert; Doerschuk, Claire M.

In: Kidney International, Vol. 46, No. 4, 10.1994, p. 1100-1109.

Research output: Contribution to journalArticle

Andreoli, S, Mallett, C, Williams, K, McAteer, JA, Rothlein, R & Doerschuk, CM 1994, 'Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury', Kidney International, vol. 46, no. 4, pp. 1100-1109.
Andreoli S, Mallett C, Williams K, McAteer JA, Rothlein R, Doerschuk CM. Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney International. 1994 Oct;46(4):1100-1109.
Andreoli, Sharon ; Mallett, Coleen ; Williams, Kathy ; McAteer, James A. ; Rothlein, Robert ; Doerschuk, Claire M. / Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. In: Kidney International. 1994 ; Vol. 46, No. 4. pp. 1100-1109.
@article{3110e3e704d44715abd54998bcfd4c34,
title = "Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury",
abstract = "To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10-7 FMLP/cylochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 ± 1.0 to 92.5 ± 7.0{\%} of the activated PMNs were adherent to mesothelial cells compared to 6 ± 1.8 to 27 ± 2.4{\%} of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41{\%} of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B. Immunohistochemical studies demonstrated that the cultured mesothelial cells express intracellular adhesion molecule 1 (ICAM-1) and FAB fragments of a monoclonal anti-ICAM-1 antibody partially reduced adhesion of activated PMNs to mesothelial cells and slightly reduced mesothelial cell injury. Staphylococcus aureus, Staphylococcus epidermidis, alpha streptococci, and Pseudomonas aeruginosa at concentrations of 103 to 105 bacteria/ml caused little to no ATP depletion or 51chromium release. We conclude that activated PMNs adhere to human mesothelial cells and induce mesothelial cell injury; such injury can be,partially reduced by blocking adhesion of activated PMNS to mesothelial cells.",
author = "Sharon Andreoli and Coleen Mallett and Kathy Williams and McAteer, {James A.} and Robert Rothlein and Doerschuk, {Claire M.}",
year = "1994",
month = "10",
language = "English",
volume = "46",
pages = "1100--1109",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury

AU - Andreoli, Sharon

AU - Mallett, Coleen

AU - Williams, Kathy

AU - McAteer, James A.

AU - Rothlein, Robert

AU - Doerschuk, Claire M.

PY - 1994/10

Y1 - 1994/10

N2 - To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10-7 FMLP/cylochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 ± 1.0 to 92.5 ± 7.0% of the activated PMNs were adherent to mesothelial cells compared to 6 ± 1.8 to 27 ± 2.4% of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41% of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B. Immunohistochemical studies demonstrated that the cultured mesothelial cells express intracellular adhesion molecule 1 (ICAM-1) and FAB fragments of a monoclonal anti-ICAM-1 antibody partially reduced adhesion of activated PMNs to mesothelial cells and slightly reduced mesothelial cell injury. Staphylococcus aureus, Staphylococcus epidermidis, alpha streptococci, and Pseudomonas aeruginosa at concentrations of 103 to 105 bacteria/ml caused little to no ATP depletion or 51chromium release. We conclude that activated PMNs adhere to human mesothelial cells and induce mesothelial cell injury; such injury can be,partially reduced by blocking adhesion of activated PMNS to mesothelial cells.

AB - To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10-7 FMLP/cylochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 ± 1.0 to 92.5 ± 7.0% of the activated PMNs were adherent to mesothelial cells compared to 6 ± 1.8 to 27 ± 2.4% of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41% of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B. Immunohistochemical studies demonstrated that the cultured mesothelial cells express intracellular adhesion molecule 1 (ICAM-1) and FAB fragments of a monoclonal anti-ICAM-1 antibody partially reduced adhesion of activated PMNs to mesothelial cells and slightly reduced mesothelial cell injury. Staphylococcus aureus, Staphylococcus epidermidis, alpha streptococci, and Pseudomonas aeruginosa at concentrations of 103 to 105 bacteria/ml caused little to no ATP depletion or 51chromium release. We conclude that activated PMNs adhere to human mesothelial cells and induce mesothelial cell injury; such injury can be,partially reduced by blocking adhesion of activated PMNS to mesothelial cells.

UR - http://www.scopus.com/inward/record.url?scp=0028063610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028063610&partnerID=8YFLogxK

M3 - Article

VL - 46

SP - 1100

EP - 1109

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -