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Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme

¹Department of Physiology, University of Bergen, N-5009 Bergan, Norway; and ²Department of Medical Biochemistry and Microbiology, University of Uppsala, S-751 23 Uppsala, Sweden

Submitted 26 September 2003 ; accepted in final form 2 November 2003

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.

N-deacetylase/N-sulfotransferase-2; mast cell; capsaicin; peptides; micropuncture

This article has been cited by other articles:

				T. V. Karlsen, A. Bletsa, E.-A. B. Gjerde, and R. K. Reed Lowering of interstitial fluid pressure after neurogenic inflammation in mouse skin is partly dependent on mast cells Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1821 - H1827. [Abstract] [Full Text] [PDF]