Human neutrophil Fc receptor-mediated adhesion under flow: a hollow fibre model of intravascular arrest.
Human polymorphonuclear cells (PMN) were found to adhere to a novel model of blood vessel wall-associated IgG. The internal surfaces of cellulose acetate hollow fibres, of comparable internal diameter to small blood vessels, were coated with normal serum human IgG, heat-aggregated IgG (HAIgG), laminin or fibrinogen. Under conditions of flow mimicking those in a small vessel, PMN were found to adhere markedly only to immunoglobulin-coated fibres. Arrest on HAIgG was inhibited by excess soluble IgG but not by bovine serum albumin (BSA), demonstrating that the adhesion was IgG-specific and presumably mediated by Fc gamma R on the PMN surface. Pre-adsorption of serum components onto HAIgG-coated fibres enhanced PMN arrest, due most probably to fixation of complement components by immobilized HAIgG, resulting in additional potential to entrap PMN via complement receptors such as CR3. Treatment of PMN with the regulatory neuropeptide substance P also enhanced adhesion to HAIgG-coated fibres and caused increased surface expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII. A mouse cell line derived from L cells, hR4C6, stably transfected with human Fc gamma RII, was found to adhere under flow to HAIgG-coated fibres, whilst untransfected parent L cells did not. This adhesion was similarly inhibited by excess soluble IgG, confirming the capability of Fc gamma R to mediate cell arrest. The study strongly suggests that Fc gamma R may play an important role in intravascular PMN arrest and we speculate that in inflammatory diseases PMN may adhere via Fc gamma R to immobilized immunoglobulin on the vascular endothelium, with subsequent degranulation and tissue damage.
D'Arrigo
C
C
Department of Pathology, University of Dundee, Ninewells Hospital, UK.
Candal-Couto
J J
JJ
Greer
M
M
Veale
D J
DJ
Woof
J M
JM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D018056:Hemorheology; D006801:Humans; D066298:In Vitro Techniques; D007739:L Cells; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D011961:Receptors, Fc / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*; D014162:Transfection
D011961:Receptors, Fc; D013373:Substance P