Enhancement of the function of neutrophil type-1 and type-3 complement receptors by human leukocyte inhibitory factor (LIF).
The lymphokine leukocyte inhibitory factor (LIF) has previously been documented to enhance several neutrophil (PMN) functions, including stimulated chemotaxis and superoxide generation, phagocytosis and adherence of opsonized targets, and antibody-dependent cellular cytotoxicity. The present studies were designed to investigate the effects of LIF on PMN function mediated by the complement components C3b and C3bi. LIF induced a dose-dependent increase in superoxide production generated by opsonized zymosan (up to 97.1 +/- 31.4% at 16 U LIF/ml; P less than 0.01). While neither control nor LIF-treated PMN were capable of inducing phagocytosis of either C3b- or C3bi-opsonized sheep erythrocytes (E) directly, exposure to LIF caused a significant (P less than 0.05) increase in their adherence to E (137.4 and 59.4%, respectively). Specificity for complement receptor function was confirmed by the ability of anti-CR1 antibody to block adherence of LIF-treated PMN to EAC3b (77.0% inhibition) and anti-CR3 antibody to block adherence to EAC3bi (70.2% inhibition). Increased C3b and C3bi function may have been due, at least in part, to increased expression of their respective surface membrane receptors. Thus, using indirect immunofluorescence, LIF induced a 38.2% increase in fluorescence of the anti-CR1 antibody and a 96.1% increase in anti-CR3 binding. These studies describe an additional mechanism through which LIF may have an important pro-inflammatory role in vivo.
Borish
L
L
Allergy Division, New England Medical Center, Boston, Massachusetts 02111.
Audera
C
C
Rosenbaum
R
R
Rocklin
R E
RE
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D005434:Flow Cytometry; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b; D012397:Rosette Formation; D013481:Superoxides / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D008222:Lymphokines; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C010598:leukocyte inhibitory factor; D013481:Superoxides