TY - JOUR
T1 - Constitutive Shedding of Both p55 and p75 Murine TNF Receptors in Vivo
AU - Pinckard, J. Keith
AU - Sheehan, Kathleen C.F.
AU - Arthur, Cora D.
AU - Schreiber, Robert D.
PY - 1997/4/15
Y1 - 1997/4/15
N2 - Recently, we reported the generation and characterization of hamster mAbs specific for the murine p55 and p75 TNF receptors. Upon characterizing these mAbs in vivo, we discovered that administration of TNF receptor-specific mAb to normal mice resulted in the linear accumulation of the appropriate class of soluble TNF receptor in the circulation. The mechanism underlying soluble receptor accumulation was found to be due to an abrogation of the clearance of constitutively shed soluble receptor by receptor-specific mAb. Levels of p55 or p75 accumulated in the presence of nonblocking, nonagonistic TNF receptor mAb were capable of inhibiting murine TNF-induced responses in vivo. These results document that both p55 and p75 are constitutively shed in substantial amounts in vivo and suggest that the process of constitutive TNF receptor shedding plays an important role in regulating TNF activity under physiologic conditions.
AB - Recently, we reported the generation and characterization of hamster mAbs specific for the murine p55 and p75 TNF receptors. Upon characterizing these mAbs in vivo, we discovered that administration of TNF receptor-specific mAb to normal mice resulted in the linear accumulation of the appropriate class of soluble TNF receptor in the circulation. The mechanism underlying soluble receptor accumulation was found to be due to an abrogation of the clearance of constitutively shed soluble receptor by receptor-specific mAb. Levels of p55 or p75 accumulated in the presence of nonblocking, nonagonistic TNF receptor mAb were capable of inhibiting murine TNF-induced responses in vivo. These results document that both p55 and p75 are constitutively shed in substantial amounts in vivo and suggest that the process of constitutive TNF receptor shedding plays an important role in regulating TNF activity under physiologic conditions.
UR - http://www.scopus.com/inward/record.url?scp=0031569611&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.158.8.3869
DO - 10.4049/jimmunol.158.8.3869
M3 - Article
C2 - 9103455
AN - SCOPUS:0031569611
SN - 0022-1767
VL - 158
SP - 3869
EP - 3873
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -