Xp. Li et al., LFA-1 AND 1-SELECTIN REGULATION OF RECIRCULATING LYMPHOCYTE TETHERINGAND ROLLING ON LUNG MICROVASCULAR ENDOTHELIUM, American journal of respiratory cell and molecular biology, 14(4), 1996, pp. 398-406
Recirculating lymphocytes migrate into areas of lung inflammation by b
inding to microvascular endothelium and transmigrating into extravascu
lar tissue. In this report, we examined the multiple-step paradigm usi
ng a unique system: recirculating lymphocytes from sheep peripheral ly
mphatics adhering to activated lung microvascular endothelium in condi
tions of physiologic flow. Video microscopy demonstrated that recircul
ating lymphocytes formed abrupt adhesions, without requisite rolling,
on the lung microvascular endothelial cells. Lymphocyte velocity was u
nchanged within 100 ms of the development of firm adhesions. To dissec
t the adhesion mechanism, the lymphocytes were pretreated with anti-LF
A-1 or anti-L-selectin monoclonal antibody (mAb). Both mAb decreased t
he incidence of firm adhesions. The mechanism of this inhibition was i
nvestigated using time-lapse topographic reconstructions of cell movem
ent after pretreatment with mAb. Time-lapse analysis of the movement o
f lymphocytes pretreated with anti-LFA-1 mAb suggested that abortive a
dhesion was manifested by a characteristic saltatory movement and a su
stained reduction in cell velocity (rolling) to < 25 mu m/s. In contra
st, abortive adhesions of lymphocytes pretreated with anti-L-selectin
mAb demonstrated transient arrest (tethering) but minimal rolling befo
re resumption of baseline velocity in the flow stream. These observati
ons provide insights into selectin and integrin regulation of lymphocy
te transmigration into the lung. Further, the results of mAb inhibitio
n suggest that the mechanism of lymphocyte migration may have some uni
que features not observed in studies of neutrophil transmigration.