| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
U.S. Department of Agriculture, Agricultural Research Service (T.H.E., S.K., R.F.), Beltsville, Maryland 20705; the Department of Physiology and Pharmacology, Auburn University (J.L.S.), Auburn, Alabama 36849; and the Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health (A.M., L.M., R.P., M.J.M., F.C.), Bethesda, Maryland 20892
Address all correspondence and requests for reprints to: Dr. Ted H. Elsasser, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, Maryland 20705. E-mail: elsasser{at}lpsi.barc.usda.gov
Rapid onset metabolic impairments accompany the initiation of the acute
phase response to many disease stresses, whereas more chronic metabolic
perturbations may prolong the recovery period. In the present
experiment the application of a mild endotoxin challenge
[lipopolysaccharide (LPS)] alone or additive to a chronic subclinical
parasitic infection (Sarcocystis cruzi; LPS + PI) in
calves was used as a model to investigate and define a dynamic axis
coordinated between adrenomedullin (AM) and nitric oxide in response to
immune challenge. Plasma AM and NO2/NO3
concentration responses after LPS (0.45 µg/kg, iv) were rapid in
onset and of higher magnitude and longer duration in PI + LPS calves
than in those challenged with LPS alone. The post-LPS increase in
plasma insulin was significantly greater in PI + LPS than in LPS;
following refeeding of calves, insulin secretion was most blunted in PI
+ LPS calves, consistent with the inhibitory effects of NO and AM on
insulin secretion. A more chronic response to the immune challenge
(organ specific) was in evidence in tissues harvested 24 h after
LPS challenge. Where lung and liver showed no immunostaining for
inducible nitric oxide (iNOS), iNOS immunostaining was present in the
pancreas, localized to islets only. The percentages of
iNOS-immunopositive cells in islets were 1.7%, 21%, 6.7%, and 24%
for control (C; saline infused), PI, LPS, and PI + LPS calves,
respectively. AM immunostaining was not evident in the liver and was
present, but not differentially affected by treatment, in airway
epithelium in the lung. The number of islet cells with positive
immunostaining for AM was increased in LPS, PI, and PI + LPS calves.
The percentages of AM-immunopositive cells in islets were 8%, 27%,
20%, and 33% for C, PI, LPS, and PI + LPS, respectively.
Immunostaining for AM and iNOS was colocalized with cells positive for
pancreatic polypeptide. By triple label confocal fluorescence
immunocytochemistry, colocalization of intense AM and iNOS
immunostaining was confirmed in peripheral islet cells. A weaker, more
diffuse iNOS signal was also apparent in insulin-containing cells in PI
+ LPS. We conclude that chronic low level infection potentiates the
severity of metabolic perturbations that arise with additive sudden
onset immune challenge, as can occur with bacterial toxins. These
metabolic disturbances are reflected in and possibly mediated by early
onset increases in plasma tumor necrosis factor-
, insulin, and AM
and up-regulated iNOS activity. These acute complications rapidly
progress into a more chronic state characterized by diminished insulin
response to feeding stimulus and colocalized increases in pancreatic
islet AM and iNOS. The pancreatic responses in AM and iNOS may play a
major role in mediating prolonged disturbances in nutrient use by
tissues through their influences on temporal patterns of pancreatic
hormone secretion during chronic illness.
This article has been cited by other articles:
 |
|
 |
|
  T. H. Elsasser, T. J. Caperna, C-J. Li, S. Kahl, and J. L. Sartin Critical control points in the impact of the proinflammatory immune response on growth and metabolism J Anim Sci, April 1, 2008; 86(14_suppl): E105 - E125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Elsasser, J. W. Blum, and S. Kahl Characterization of calves exhibiting a novel inheritable TNF-{alpha} hyperresponsiveness to endotoxin: associations with increased pathophysiological complications J Appl Physiol, June 1, 2005; 98(6): 2045 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. F. Wong, B. M. Y. Cheung, Y.-Y. Li, and F. Tang Adrenomedullin Is Both Proinflammatory and Antiinflammatory: Its Effects on Gene Expression and Secretion of Cytokines and Macrophage Migration Inhibitory Factor in NR8383 Macrophage Cell Line Endocrinology, March 1, 2005; 146(3): 1321 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Kim, S.-O. Moon, S. Lee, M. J. Sung, S. H. Kim, and S. K. Park Adrenomedullin Reduces VEGF-Induced Endothelial Adhesion Molecules and Adhesiveness Through a Phosphatidylinositol 3'-Kinase Pathway Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1377 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Garmendia, M. P. Rodriguez, M. A. Burrell, and A. C. Villaro Immunocytochemical Finding of the Amidating Enzymes in Mouse Pancreatic A-, B-, and D-cells: A Comparison with Human and Rat J. Histochem. Cytochem., October 1, 2002; 50(10): 1401 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Martinez, S. Kapas, M.-J. Miller, Y. Ward, and F. Cuttitta Coexpression of Receptors for Adrenomedullin, Calcitonin Gene-Related Peptide, and Amylin in Pancreatic {beta}-Cells Endocrinology, January 1, 2000; 141(1): 406 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pio, A. Martinez, E. J. Unsworth, J. A. Kowalak, J. A. Bengoechea, P. F. Zipfel, T. H. Elsasser, and F. Cuttitta Complement Factor H Is a Serum-binding Protein for Adrenomedullin, and the Resulting Complex Modulates the Bioactivities of Both Partners J. Biol. Chem., April 6, 2001; 276(15): 12292 - 12300. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
