P-selectin interacts with a beta 2-integrin to enhance phagocytosis.
P-selectin is an adhesion molecule for myeloid cells that seems to be essential for the development of cellular inflammatory responses. We show that adhesion of neutrophils to purified and recombinant P-selectin enhances the phagocytosis of unopsonized zymosan particles as judged by the number of cells ingesting particles (30.2 +/- 5.8 vs 14.5 +/- 4.0, p = 0.002) and the number of particles ingested per cell (percentage increase 58.3 +/- 4.4%. p = 0.0002). The enhanced phagocytosis was inhibited by Abs to CD18 or CD11b, suggesting that P-selectin alters beta 2-integrin function. The enhancement was only seen in the presence of cations allowing the integrin to assume a particular extracellular conformation. Furthermore, P-selectin, although not altering the total expression of CD18 on neutrophils, significantly increased the binding of mAb 24, which detects an activation-dependent epitope. Our results support a signaling role for P-selectin in influencing beta 2-integrin function.
Cooper
D
D
Hanson Center for Cancer Research, Institute for Medical and Veterinary Science, Adelaide, Australia.
Butcher
C M
CM
Berndt
M C
MC
Vadas
M A
MA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens; D016466:CHO Cells; D002413:Cations, Divalent / Q000494:pharmacology; D006224:Cricetinae; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin; D010587:Phagocytosis / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011994:Recombinant Proteins; D013820:Thermolysin / Q000494:pharmacology
D015703:Antigens, CD; D018821:CD18 Antigens; D002413:Cations, Divalent; D000939:Epitopes; D016023:Integrins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D013820:Thermolysin