PMID- 15576666
OWN - NLM
STAT- MEDLINE
DCOM- 20050415
LR  - 20200930
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 288
IP  - 4
DP  - 2005 Apr
TI  - Albumin is not an irreplaceable carrier for amphipathic mediators of 
      thermoregulatory responses to LPS: compensatory role of alpha1-acid glycoprotein.
PG  - R872-8
AB  - In view of the potential involvement of peripherally synthesized, circulating 
      amphipathic mediators [such as platelet-activating factor (PAF) and prostaglandin 
      E(2)] in the systemic inflammatory response to lipopolysaccharide (LPS), we 
      hypothesized that transport of amphipaths by albumin is essential for conveying 
      peripheral inflammatory signals to the brain. Our first specific aim was to test 
      this hypothesis by studying LPS-induced fever and hypothermia in Nagase 
      analbuminemic rats (NAR). NAR from two different colonies and normalbuminemic 
      Sprague-Dawley rats were preimplanted with jugular catheters, and their febrile 
      responses to a mild dose of LPS (10 microg/kg i.v.) at thermoneutrality and 
      hypothermic responses to a high dose of LPS (500 microg/kg i.v.) in the cold were 
      studied. NAR of both colonies developed normal febrile and hypothermic responses, 
      thus suggesting that transport of amphipathic mediators by albumin is not 
      indispensable for LPS signaling. Although alternative carrier proteins [such as 
      alpha(1)-acid glycoprotein (AGP)] are known to assume transport functions of 
      albumin in NAR, it is unknown whether inflammatory mediators are capable of 
      inducing their actions when bound to alternative carriers. To test whether PAF, 
      the most potent amphipathic pyrogen, causes fever when administered in an 
      AGP-bound form was our second aim. Sprague-Dawley rats were preimplanted with 
      jugular catheters, and their thermal responses to infusion of a 1:1 [PAF-AGP] 
      complex (40 nmol/kg i.v.), AGP (40 nmol/kg i.v.), or various doses of free 
      (aggregated) PAF were studied. The complex, but neither free PAF nor AGP, caused 
      a high ( approximately 1.5 degrees C) fever with a short (< 10 min) latency. This 
      is the first demonstration of a pyrogenic activity of AGP-bound PAF. We conclude 
      that, in the absence of albumin, AGP and possibly other carriers participate in 
      immune-to-brain signaling by binding and transporting amphipathic inflammatory 
      mediators.
FAU - Ivanov, Andrei I
AU  - Ivanov AI
AD  - Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and 
      Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USA.
FAU - Steiner, Alexandre A
AU  - Steiner AA
FAU - Patel, Shreya
AU  - Patel S
FAU - Rudaya, Alla Y
AU  - Rudaya AY
FAU - Romanovsky, Andrej A
AU  - Romanovsky AA
LA  - eng
GR  - R01 NS-41233/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041202
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Carrier Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Orosomucoid)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Serum Albumin)
SB  - IM
MH  - Animals
MH  - Body Temperature Regulation/drug effects/*physiology
MH  - Carrier Proteins/*metabolism
MH  - Fever/chemically induced/physiopathology
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Orosomucoid/*metabolism
MH  - Platelet Activating Factor/metabolism/physiology
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serum Albumin/*metabolism
EDAT- 2004/12/04 09:00
MHDA- 2005/04/16 09:00
CRDT- 2004/12/04 09:00
PHST- 2004/12/04 09:00 [pubmed]
PHST- 2005/04/16 09:00 [medline]
PHST- 2004/12/04 09:00 [entrez]
AID - 00514.2004 [pii]
AID - 10.1152/ajpregu.00514.2004 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R872-8. doi: 
      10.1152/ajpregu.00514.2004. Epub 2004 Dec 2.