Human alveolar macrophages prevent apoptosis in polymorphonuclear
leukocytes.
Herlihy, J. Patrick, Mary W. Vermeulen, and Charles A. Hales.
Pulmonary and Critical Care Unit, Massachusetts General Hospital
and Harvard Medical School, Boston, Massachusetts 02114-2698
APStracts 3:0112L, 1996.
Polymorphonuclear leukocytes (PMNs) are recruited to the lungs to
defend against injury and infection. PMNs, however, undergo
apoptosis, thereby losing functional ability within hours and die
with lysis soon thereafter unless they receive specific signals
preventing this phenomenon. We hypothesized that alveolar macrophages
(AMs) could provide these signals. Therefore, AMs, obtained through
bronchoalveolar lavage of healthy volunteers (n=9), were cultured for
24 hrs., after which the AM conditioned media (AM-CM) were removed.
Freshly isolated PMNs, which showed no apoptosis, were suspended in
AM-CM, as well as in unconditioned media (UM), and followed over 48
hrs. for apoptosis and survival. In 8 of 9 patients AM-CM contained
TNF which modestly delayed AM apoptosis so that the % of PMN
apoptotic at 24 hrs. was 77+6 in AM-CM compared to 91+2 in UM
(p<.05). In one patient urticaria developed early in the lavage
and his AM-CM profoundly prevented apoptosis of PMN to 10% at 24 hrs.
PMN survival in this patient was similarly enhanced so that at 48
hours of culture it was 60% compared to 45+8% in AM-CM and 30+6% in
mM (p<.05 UM vs. AM-CM). GM-CSF, in addition to TNF-a, partly
accounted for this medium's activity. Thus, AMs can delay apoptosis
in PMNs through production of TNF-[alpha] and in some cases by GM
-CSF. When activated in vivo by conditions such as an allergic
reaction, AM can rapidly and profoundly suppress PMN apoptosis.
Received 13 November 1995; accepted in final form 17 June 1996.
APS Manuscript Number L328-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996