HUMAN MONOCYTE-DERIVED MACROPHAGE PHAGOCYTOSIS OF SENESCENT EOSINOPHILS UNDERGOING APOPTOSIS - MEDIATION BY ALPHA(V)BETA(3) CD36/THROMBOSPONDIN RECOGNITION MECHANISM AND LACK OF PHLOGISTIC RESPONSE/
M. Stern et al., HUMAN MONOCYTE-DERIVED MACROPHAGE PHAGOCYTOSIS OF SENESCENT EOSINOPHILS UNDERGOING APOPTOSIS - MEDIATION BY ALPHA(V)BETA(3) CD36/THROMBOSPONDIN RECOGNITION MECHANISM AND LACK OF PHLOGISTIC RESPONSE/, The American journal of pathology, 149(3), 1996, pp. 911-921
Eosinophils may mediate tissue injury in a number of allergic diseases
, Previously, we reported that eosinophils constitutively undergo apop
tosis (programed cell death) in culture. As this led to phagocytosis o
f the intact senescent cell by macrophages, we proposed that apoptosis
represented an injury-limiting eosinophil disposal mechanism. Ingesti
on of apoptotic neutrophils by human monocyte-derived macrophages (MOs
) was found to be mediated by adhesive interactions between thrombospo
ndin and the MO alpha(v) beta(3) vitronectin receptor integrin and MO
CD36. As this failed to elicit a pro-inflammatory response from MOs, w
e sought evidence that this specific, nonphlogistic clearance mechanis
m may operate in eosinophil disposal, In this study, we found that MO
ingestion of apoptotic eosinophils was specifically, inhibited by mono
clonal antibodies to MO alpha(v) beta(3), CD36, and thrombospondin and
by other inhibitors of this recognition mechanism including RGD pepti
de and amino sugars. Furthermore, not only did MO ingestion of intact
apoptotic eosinophils fail to stimulate release of the phlogistic eico
sanoid thromboxane, but there was also a lack of increased release of
the pro-inflammatory cytokine granulocyte/macrophage colony-stimulatin
g factor, However, increased release of these mediators was observed w
hen MOs took up senescent post-apoptotic eosinophils that had been cul
tured long enough to lose plasma membrane integrity. The data indicate
that the nonphlogistic alpha(v) beta(3)/CD3G/thrombospondin macrophag
e recognition mechanism is available for clearance of intact senescent
eosinophils undergoing apoptosis, Furthermore, our findings suggest t
hat, by contrast, plagocytosis of post-apoptotic eosinophils may elici
t undesirable pro-inflammatory responses.