Fever-range temperature stimulates MAdCAM-1–dependent adhesion in PP HEV during WBH treatment in vivo and in organ cultures in vitro.

(A,B) PP or pancreatic tissues were isolated from normothermal controls (core temperature of controls [C] was 36.8 ± 0.2°C) or mice treated 6 hours with WBH (39.7 ± 0.2°C). Tissues were cryopreserved and used in adhesion assays. (A) Selected tissue cryosections were blocked with the MAdCAM-1–specific mAb MECA-367. (B) Cells were either untreated or treated with DATK32 mAb or DREG-56 mAb. (C) Bilateral pairs of PLN were isolated from normothermic BALB/c mice, separated into 2 groups, and cultured for 6 hours in 1 mL complete medium at 37°C or 40°C in a 5% carbon dioxide incubator. PP collected from normothermic mouse pairs were cultured at 37°C and 40°C. Lymphoid tissues were then frozen and used in adhesion assays under shear conditions. To evaluate L-selectin–dependent adhesion of human PBL to PLN HEV, assays were performed without antibody or in the presence of function-blocking mAb (DREG-56 or MECA-79). To quantify α4β7 integrin/MAdCAM-1–dependent adhesion in PP organ cultures, adherence of TK1 indicator cells to HEV was evaluated without antibody or in the presence of DATK32 mAb or MECA-367 mAb. Data represent the mean ± SE values from 3 independent experiments. * indicates significant differences for the increase in HEV adhesion detected in response to hyperthermia (P < .0001 by unpaired 2-tailed Student t test).