NEISSERIAL PORINS INHIBIT HUMAN NEUTROPHIL ACTIN POLYMERIZATION, DEGRANULATION, OPSONIN RECEPTOR EXPRESSION, AND PHAGOCYTOSIS BUT PRIME THENEUTROPHILS TO INCREASE THEIR OXIDATIVE BURST

Porins are trimeric proteins that constitute water-filled pores that a llow transmembrane diffusion of small solutes through the outer membra ne layer of gram-negative bacteria. The porins are capable of insertin g into the membranes of eucaryotic cells, and in the present study we have examined the in vitro effects on neutrophil functions of the foll owing purified porins: meningococcal outer membrane protein classes 1 and 3 and gono-coccal outer membrane protein 1B (P1B). The neisserial porins inhibited human neutrophil chemoattractant induced actin polyme rization and degranulation of both primary and secondary granules. The neutrophil expression of immunoglobulin G (IgG) Fe receptors II (Fc g amma RII; CDw32) and III (Fc gamma RIII; CD16), as well as the activat ion-dependent downregulation of Fc gamma RIII, were reduced by the men ingococcal and gonococcal porins. The neisserial porins impaired the u pregulation of complement receptors 1 (CD35) and 3 (CD11b) and inhibit ed the phagocytic capacity of neutrophils, as evaluated by the uptake of meningococci (strain 44/76) in the presence of patient serum contai ning known amounts of IgG against meningococcal porins. The porins als o primed neutrophils to increase their intracellular hydrogen peroxide production in response to FMLP, whereas no such priming was observed if the neutrophil protein kinase C was stimulated directly with phorbo l myristate acetate. The neisserial porins influenced neutrophil funct ions in a time- and concentration-dependent manner. The meningococcal class 1 outer membrane protein and the gonococcal P1B tended to alter neutrophil functions more than the meningococcal class 3 protein. Thus , the neisserial porins inhibited human neutrophil actin polymerizatio n, degranulation, opsonin receptor expression, and phagocytosis but pr imed the neutrophils to increase their oxidative burst. It remains to be determined whether these in vitro observations reflect mechanisms t hat may be of importance for the interaction between neutrophils and N eisseria species in vivo.