Our research program focusses on the understanding and elucidation of the role and functional responsiveness of human neutrophils. These cells play are critically involved in as yet incompletely characterized ways in the defense of the organism against pathogenic aggressions and injury. They continuously patrol the body and are equipped to detect and respond to infectious organisms as well as cell debris. In addition, recent data indicate that they play critical roles in the initiation and control of the subsequent immune response.

Our approach is based on the premiss that the outlining of the events leading to the proper accomplishment of a cell function can, in the final analysis, only be derived from the examination of these events in the primary cell. Accordingly, we focus on human peripheral blood neutrophils in which we attempt to dissect the sequence of events that lead from the surface recognition of various pathophysiologically relevant stimuli to the performance of the appropriate function. These studies are complemented by cell line-based experiments in those situations where the latter allow the examination of otherwise unapproachable questions. The emphasis in all of these studies is on deriving information about causative relationships.

Barabe, F., Rollet-Labelle, E., Gilbert, C., Fernandes, M.J., Naccache, S.N., and Naccache, P.H. 2002. Early events in the activation of Fc gamma RIIA in human neutrophils: stimulated insolubilization, translocation to detergent-resistant domains, and degradation of Fc gamma RIIA. J Immunol168:4042-4049.

Naccache, P.H., Levasseur, S., Lachance, G., Chakravarti, S., Bourgoin, S.G., and McColl, S.R. 2000. Stimulation of human neutrophils by chemotactic factors is associated with the activation of phosphatidylinositol 3-kinase gamma. J. Biol. Chem.275:23636-23641.

Lachance, G., Levasseur, S., and Naccache, P.H. 2002. Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. Implication of phosphatidynositol 3-kinases. J Biol Chem277:21537-21541.

Damaj, B.B., McColl, S.R., Neote, K., Na, S.Q., Ogborn, K.T., Hebert, C.A., and Naccache, P.H. 1996. Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops. FASEB Journal10:1426-1434.

Barabé, F., Gilbert, C., Liao, N., Bourgoin, S.G., and Naccache, P.H. 1998. Crystal-induced neutrophil activation VI. Involvement of Fc gamma RIIIB (CD16) and CD11b in response to inflammatory microcrystals. FASEB J.12:209-220.