title: Leishmania major-human macrophage interactions: cooperation between Mac-1 (CD11b/CD18) and complement receptor type 1 (CD35) in promastigote adhesion.
abstract: It has been suggested that the developmental maturation of Leishmania major promastigotes can affect their interaction with human complement receptors. To study this, we measured the adhesion of metacyclic and logarithmic-phase L. major promastigotes to complement receptors expressed on primary macrophages, to recombinant receptors expressed on transfected cells, or to purified complement receptors in a cell-free system. We demonstrate that complement-opsonized promastigotes can bind to both Mac-1 and complement receptor type 1 (CR1) and that the transition of promastigotes from the noninfectious logarithmic phase of growth to the infectious metacyclic stage does not affect this interaction. Furthermore, we show that Mac-1 and CR1 can cooperate to mediate the efficient adhesion of complement-opsonized metacyclic promastigotes to cells expressing both receptors. On human monocyte-derived macrophages, Mac-1 appears to make a quantitatively greater contribution to this adhesion than does CR1, since blocking macrophage Mac-1 diminishes metacyclic promastigote adhesion to a greater extent than does blocking CR1. In addition, bovine monocytes lacking Mac-1 exhibit a dramatic decrease in complement-dependent promastigote adhesion, relative to normal monocytes. The predominance of Mac-1 in these interactions is due, at least in part, to the factor I cofactor activity of CR1, which facilitates the conversion of C3b to iC3b. The stable adhesion of complement-opsonized metacyclic promastigotes to Mac-1 is a prerequisite for phagocytosis by human monocyte-derived macrophages. Blocking Mac-1 on macrophages abrogates the majority of the complement-dependent phagocytosis of promastigotes, whereas blocking CR1 has no detectable effect on phagocytosis. In addition, bovine monocytes lacking Mac-1 exhibit a dramatic reduction in promastigote phagocytosis relative to normal bovine monocytes. We conclude, therefore, that the two complement receptors, Mac-1 and CR1, can cooperate to mediate the initial complement-dependent adhesion of metacyclic promastigotes to human monocyte-derived macrophages and that Mac-1 is the predominant complement receptor responsible for the phagocytosis of complement-opsonized metacyclic promastigotes.
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Rosenthal
authors.forename: F S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: M E
authors.initials: ME
authors.lastname: Kehrli
authors.forename: D M
authors.initials: DM
authors.lastname: Mosser
mesh_terms: D000268:Adhesiveness; D000328:Adult; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D018320:Leishmania major / Q000276:immunology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D010587:Phagocytosis; D017463:Receptors, Complement 3b / Q000502:physiology*
chemical_list: D016177:Macrophage-1 Antigen; D017463:Receptors, Complement 3b; D005340:Fibrinogen