p85α subunit of class IA PI-3 kinase is crucial for macrophage growth and migration

Veerendra Munugalavadla, Jovencio Borneo, David Ingram, Reuben Kapur

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Macrophages play an essential role in defending against invading pathogens by migrating to the sites of infection, removing apoptotic cells, and secreting inflammatory cytokines. The molecular mechanisms whereby macrophages regulate these processes are poorly understood. Using bone marrow-derived macrophages (BMMs) deficient in the expression of p85α-subunit of class IA phosphatidylinositol 3 (PI-3) kinase, we demonstrate 50% reduction in proliferation in response to macrophage-colony-stimulating factor (M-CSF) as well as granulocyte macrophage-colony-stimulating factor (GM-CSF) compared with wild-type controls. Furthermore, p85α-/- BMMs demonstrate a significant reduction in migration in a wound-healing assay compared with wild-type controls. The reduction in migration due to p85α deficiency in BMMs is associated with reduced adhesion and directed migration on fibronectin and vascular cell adhesion molecule-1. In addition, deficiency of p85α in BMMs also results in defective phagocytosis of sheep red blood cells. Biochemically, loss of p85α in BMMs results in reduced activation of Akt and Rac, but not Erk (extracellular signal-related kinase) mitogen-activated protein (MAP) kinase. Taken together, our results provide genetic evidence for the importance of p85α in regulating both actin- and growth-based functions in macrophages, and provide a potential therapeutic target for the treatment of diseases involving macrophages, including inflammation.

Original languageEnglish
Pages (from-to)103-109
Number of pages7
JournalBlood
Volume106
Issue number1
DOIs
StatePublished - Jul 1 2005

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Phosphatidylinositol 3-Kinase
Macrophages
Growth
Bone
Cells
Macrophage Colony-Stimulating Factor
Vascular Cell Adhesion Molecule-1
Granulocyte-Macrophage Colony-Stimulating Factor
Mitogen-Activated Protein Kinases
Fibronectins
Phagocytosis
Pathogens
Wound Healing
Actins
Sheep
Phosphotransferases
Erythrocytes
Assays
Blood
Adhesion

ASJC Scopus subject areas

  • Hematology

Cite this

p85α subunit of class IA PI-3 kinase is crucial for macrophage growth and migration. / Munugalavadla, Veerendra; Borneo, Jovencio; Ingram, David; Kapur, Reuben.

In: Blood, Vol. 106, No. 1, 01.07.2005, p. 103-109.

Research output: Contribution to journalArticle

Munugalavadla, Veerendra ; Borneo, Jovencio ; Ingram, David ; Kapur, Reuben. / p85α subunit of class IA PI-3 kinase is crucial for macrophage growth and migration. In: Blood. 2005 ; Vol. 106, No. 1. pp. 103-109.
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