title: Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme.
abstract: Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P(if)) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2(-/-)). P(if) and PPE were measured after challenge with compound 48/80 (C48/80), and P(if) alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P(if) in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P(if) significantly (P < 0.05) in NDST-2(-/-) mice (-1.67 +/- 0.42 mmHg) compared with vehicle (-0.57 +/- 0.17 mmHg) but the lowering was significantly (P < 0.05) less compared with that of the NDST-2(+/+) mice (-2.31 +/- 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2(+/+) mice, whereas there was no increase in PPE in NDST-2(-/-) mice. Capsaicin, SP, and CGRP lowered P(if) significantly (P < 0.05) compared with vehicle and to the same extent in both NDST-2(+/+) and NDST-2(-/-) mice. We can conclude that although NDST-2(-/-) mice demonstrate an altered response in P(if) after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs.
authors: Dept. of Physiology, Univ. of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. tine.karlsen@fys.uib.no
authors: Tine V
authors: TV
authors: Karlsen
authors: Vegard V
authors: VV
authors: Iversen
authors: Erik
authors: E
authors: Forsberg
authors: Lena
authors: L
authors: Kjellén
authors: Rolf K
authors: RK
authors: Reed
authors: Eli-Anne B
authors: EA
authors: Gjerde
mesh_terms: D000208:Acute Disease; D000581:Amidohydrolases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin; D045604:Extracellular Fluid / Q000502:physiology; D005260:Female; D006493:Heparin / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D012867:Skin / Q000276:immunology / Q000294:innervation; D013373:Substance P / Q000494:pharmacology; D015238:Sulfotransferases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D006493:Heparin; C491855:Ndst2 protein, mouse; D015238:Sulfotransferases; D000581:Amidohydrolases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin