+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

CR3 (Mac-1, alpha M beta 2, CD11b/CD18) and Fc gamma RIII cooperate in generation of a neutrophil respiratory burst: requirement for Fc gamma RIII and tyrosine phosphorylation

CR3 (Mac-1, alpha M beta 2, CD11b/CD18) and Fc gamma RIII cooperate in generation of a neutrophil respiratory burst: requirement for Fc gamma RIII and tyrosine phosphorylation

Journal of Cell Biology 125(6): 1407-1416

Cooperation among plasma membrane receptors in activating signal transduction cascades is not well understood. For almost 20 years, it has been clear that when a particulate foreign body is opsonized with complement as well as IgG, the efficiency of IgG effector functions is markedly enhanced. However, the molecular mechanisms involved in cooperation between IgG Fc receptors and complement receptors have not been elucidated. In this work, we show that when human neutrophils (PMN) are plated on a surface coated with both anti-CR3 and anti-Fc gamma RIII antibodies, the respiratory burst which occurs is equivalent to that stimulated by anti-Fc gamma RII. The CR3 ligand iC3b is as effective as anti-CR3 for cooperating with anti-Fc gamma RIII in generation of a respiratory burst. The synergy between CR3 and Fc gamma RIII for activating the NADPH oxidase is abolished by Fab of anti-Fc gamma RII. Nonetheless, the observed synergy is not an artifact of unintended Fc gamma RII ligation, since (a) only this combination of antibodies works to generate H2O2; (b) coating plates with either of the antibodies alone cannot activate the respiratory burst at any dose; (c) LAD (CR3 deficient) cells, which are perfectly competent to mount a respiratory burst when Fc gamma RII is engaged, are incapable of activating the respiratory burst when adherent to wells coated with anti-Fc gamma RIII and anti-CR3; (d) direct engagement of Fc gamma RII activates the respiratory burst by a pathway pharmacologically distinguishable from the synergistic respiratory burst. Fc gamma RIII/CR3 synergy is abolished by cytochalasin B and herbimicin, suggesting that both the actin cytoskeleton and tyrosine phosphorylation are necessary for activation of the synergistic respiratory burst. Further analysis shows that CR3 and Fc gamma RIII have distinct roles in activation of this Fc gamma RII-dependent assembly of the NADPH oxidase. Ligation of CR3 is sufficient to lead to Fc gamma RII association with the actin cytoskeleton on the adherent PMN surface. Coligation of Fc gamma RIII is required for tyrosine phosphorylation of Fc gamma RII. These data are consistent with a model in which phosphorylation of Fc gamma RII or a closely associated substrate initiates activation of a signal transduction pathway leading to oxidase assembly. These are the first data to demonstrate a molecular mechanism for synergy between IgG Fc and complement receptors in activation of phagocyte effector functions.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 042429155

Download citation: RISBibTeXText

PMID: 7515890

DOI: 10.1083/jcb.125.6.1407

Related references

Cr3 (Mac-1, M2, Cd11b/Cd18) and FcRiii Cooperate in Generation of a Neutrophil Respiratory Burst: Requirement for FcRii and Tyrosine Phosphorylation. The Journal of Cell Biology 125(6): 1407-1416, 1994

CR3 (Mac-1, amb2, CD11b/CD18) and FccRIII cooperate in generation of neutrophil respiratory burst: requirement for FccRII and tyrosine phosphorylation. The Journal of Cell Biology 125(6): 07-16, 1994

Fc gamma RII, Fc gamma RIII, and CD18 receptors mediate in part neutrophil activation on a plasma coated expanded polytetrafluoroethylene surface. Surgery 118(2): 154-60; Discussion 160-1, 1995

Tyrosine phosphorylation of a gamma-chain homodimer associated with Fc gamma RIII (CD16) in cultured human monocytes. Journal of Immunology 151(11): 6382-6388, 1993

Characterization of separate Fc-gamma-RIII-A but not Fc-gamma-RIII-B promoter regions responsible for the expression of novel receptor isoforms by human NK cells. 9TH INTERNATIONAL CONGRESS OF IMMUNOLOGY [Author] The 9th International Congress of Immunology : 477, 1995

Extremely low birth weight infants have lower Fc gamma RIII (CD 16) plasma levels and their PMN produce less Fc gamma RIII compared to adults. Biology of the Neonate 69(4): 235-242, 1996

Soluble Fc-gamma-RIII in plasma and total cellular Fc-gamma-RIII in polymorphonuclear leukocyte are low in infants with birth weight less than 1 250 grams. Pediatric Research 35(4 Part 2): 302A, 1994

Monocyte/macrophage Fc gamma RIII, unlike Fc gamma RIII on neutrophils, is not a phosphatidylinositol-linked protein. Blood 75(12): 2396-2400, 1990

Reactivity of cloned, expressed human Fc gamma RIII isoforms with monoclonal antibodies which distinguish cell-type-specific and allelic forms of Fc gamma RIII. International Immunology 2(4): 303-310, 1990

Fc gamma RIII (CD16) on human macrophages is a functional product of the Fc gamma RIII-2 gene. European Journal of Immunology 21(2): 425-429, 1991

Structural characterization of the human Fc-gamma-RIII-A and Fc-gamma-RIII-B gene promoters. Immunobiology 186(1-2): 159-160, 1992

Human fc gamma riii 1 and fc gamma riii 2 identification of the promoter regions. Immunobiology 183(3-4): 195, 1991

Characterization of the Fc-gamma-RIII-A and Fc-gamma-RIII-B comparative gene promoters. Natural Immunity 11(5): 282, 1992

A microscopic study of Fc gamma RIII-mediated respiratory burst in neutrophils. Immunobiology 199(1): 39-50, 1998

The anti-Fc-gamma-RIII MAb 3G8 induces neutrophil activation via a cooperative action of Fc-gamma-RIIIb and Fc-gamma-RIIa. International Journal of Biochemistry & Cell Biology 29(3): 465-473, 1997