Differential regulation of the mannose and sp-a receptors on
macrophages.
Chroneos, Zissis, and Virginia L. Shepherd.
Departments of Medicine and Biochemistry, Vanderbilt University
School of Medicine, and the Department of Veteran's Affairs,
Nashville, TN 37212
APStracts 2:0101L, 1995.
Two carbohydrate-dependent mechanisms exist on alveolar macrophages to
clear mannose-containing pathogens: receptor-mediated entry of non
-opsonized microorganisms via the mannose receptor and receptor
recognition of pathogens opsonized with surfactant-associated protein
A (SP-A). A number of studies have demonstrated that mannose receptor
expression is tightly linked to the functional state of the
macrophage. In the present study, we investigated regulation of
binding of SP-A to its receptor on macrophages by the same agents
that regulate mannose receptor expression. PMA, LPS, and IFN-_
treatment of rat marrow-derived macrophages increased SP-A binding by
163%, 296%, and 337% respectively over untreated controls. Mannose
receptor activity was reduced to 75%, 60%, and 25% of control levels
by these agents. Dexamethasone increased mannose receptor activity to
225%, while decreasing SP-A binding to 44% of controls. Addition of
GM-CSF to human monocytes on day 0 dramatically increased mannose
receptor activity on day 5 over the non-serum control. SP-A binding
was highest to freshly isolated monocytes, and decreased to less than
10% following differentiation in the presence of GM-CSF. Following
i.p. injection of dexamethasone, rat alveolar macrophages isolated at
24 hr expressed increased mannose receptor activity and decreased SP
-A binding. LPS injection resulted in increased SP-A binding and
decreased mannose receptor activity. In every instance, SP-A binding
was inversely regulated with respect to mannose receptor expression.
We therefore speculate that the mannose receptor is a first-line host
defense receptor that is turned off during inflammation. SP-A in the
alveolar space can then act as a lung-specific opsonin and mediate
clearance of pathogens via the up-regulated SP-A receptor.
Received 9 September 194; accepted in final form 22 June 1995.
APS Manuscript Number L270-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.