Dendritic cell precursors are enriched in the vascular compartment of the lung

The vast mucosal interface separating external from internal compartments o f the lung is under the surveillance of a population of blood-borne, bone m arrow-derived dendritic cells (DC) characterized by constant turnover. Beca use these sentinel cells process foreign antigens that have penetrated the epithelial barrier and transport them to local lymph nodes, they require co ntinuous replenishment by blood-borne cells. In the present study, the phen otype and function of DC and their precursors isolated from the vascular co mpartment of the lung were examined and compared with chose in vena cava bl ood. Intravascular leukocytes were retrieved by exhaustive perfusion of the lung vasculature. Leukocytes harvested from the subdiaphragmatic vena cava of the same animal served as a source of DC in prepulmonary blood. Typical , large, major histocompatibility class II+ antigen (MHC II+) DC constitute d <1% of leukocytes from either vascular compartment. These cells expressed intercellular adhesion molecule [ICAM]-1 and lymphocyte function-associate d antigen [LFA]-1 and many were ED1(+) (lysosomal antigen in monocytes, mac rophages, and some DC). No ED2(+) cells (macrophages) were identified. Very few of the circulating DC expressed; the alpha-like subunit of integrin re cognized by the OX62 monoclonal antibody. A striking difference appeared wh en neutrophil-depleted leukocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) for 3 d; the number of MHC II+ DC gener ated from pulmonary vascular leukocytes was 76% greater than that from the vena cava population. After pulse-labeling with tritiated thymidine ([H-3]T dR) followed by 3 d of culture with GM-CSF, DC from either source remained virtually unlabeled, as determined by autoradiography. On the day of harves t, DC and their precursors obtained from either vascular compartment were p oor stimulators of the mixed leukocyte reaction and required GM-CSF for dev elopment of their full accessory cell capability. These data suggest that, relative to leukocytes in vena cava blood, those in the lung vascular compa rtment are enriched in a population of mononuclear cells that are capable o f differentiating into MHC II+ DC when exposed to the appropriate growth fa ctors, including GM-CSF. This enriched population of DC precursors could re present a source from which lung DC may be readily recruited not only to re plenish the normally turning-over mucosal DC, but also to participate in in flammatory reactions occurring in the lung.