Modified skin-window technique in cynomolgus macaques (Macaca fasicularis) for assessing neutrophil extravasation.
Alterations in neutrophil extravasation are seen in disease states and in response to therapeutics. To investigate neutrophil extravasation during the acute inflammatory response, a skin-window technique used in humans was adapted for use in cynomolgus macaques (Macaca fasicularis). Modulation of neutrophil extravasation was attempted with systemic methotrexate and local application of the anaphylatoxin recombinant C5a (rC5a). On day 1, skin windows were created in 4 ketamine-anesthetized monkeys on both forearms by mildly abrading the skin and then overlaying the abrasions with filter paper either saturated in saline or rC5a for 6 h. At 2.5 h prior to generation of new skin windows on day 2, the monkeys received 4.5 mg methotrexate IM, and skin windows and treatment with saline or rC5a were repeated on new forearm sites on each monkey. All papers were analyzed for albumin, neutrophil number, and the neutrophil chemoattractant IL8. Day 1 albumin levels did not differ between groups, indicating consistent abrasion. Methotrexate given prior to the day 2 abrasions reduced neutrophil extravasation and IL8 levels compared with those on day 1. rC5a partially abrogated the methotrexate-induced reduction in neutrophil extravasation and IL8 production. The skin-window technique was well tolerated by the monkeys and successfully accommodated measurement of changes in neutrophil extravasation in response to inflammatory modulators.
Maguire
Sean
S
Laboratory Animal Science, GlaxoSmithKline, King of Prussia, Pennsylvania, USA. sean.x.maguire@gsk.com
Dobrzynski
Eric
E
Alpaugh
R Katherine
RK
D000818:Animals; D040881:CD11a Antigen / Q000378:metabolism; D008252:Macaca fascicularis; D008727:Methotrexate / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012884:Skin Window Technique / Q000009:adverse effects / Q000379:methods / Q000662:veterinary*
D040881:CD11a Antigen; D008727:Methotrexate
J Clin Invest. 1985 Feb;75(2):486-95
2982914
Arthritis Rheum. 1988 Mar;31(3):305-14
2965875
Arthritis Rheum. 1998 Nov;41(11):2032-8
9811059
Scand J Immunol. 1985 Dec;22(6):597-602
3937224
J Exp Med. 1998 Mar 16;187(6):903-15
9500793
J Immunol Methods. 2001 Nov 1;257(1-2):213-20
11687254
Semin Cutan Med Surg. 2003 Sep;22(3):187-95
14649586
J Rheumatol. 1987 Feb;14(1):9-11
3033240
J Clin Oncol. 1985 Mar;3(3):415-9
3973653
Immunology. 1993 Feb;78(2):197-204
8473013
Burns. 1999 Aug;25(5):403-10
10439148
J Immunol Methods. 1987 Nov 5;103(2):267-73
3312417
Infect Immun. 1995 Apr;63(4):1507-15
7890417
Trends Immunol. 2003 Jun;24(6):327-34
12810109
Acta Derm Venereol Suppl (Stockh). 1985;120:23-6
3869414
J Lab Clin Med. 1975 Dec;86(6):1040-6
1104726
Annu Rev Immunol. 2005;23:821-52
15771587
J Lab Clin Med. 1969 Nov;74(5):742-56
4900337
J Clin Invest. 1993 Dec;92(6):2675-82
8254024
J Invest Dermatol. 1987 Aug;89(2):192-6
3598210
Rheumatol Int. 1988;8(1):41-5
3363283
Ann N Y Acad Sci. 1955 Mar 24;59(5):757-805
13259351
J Clin Pharm Ther. 1990 Apr;15(2):89-95
2187892
FEBS Lett. 1992 Jul 27;307(1):97-101
1639201
Br J Dermatol. 1994 Jun;130(6):725-30
8011497
J Invest Dermatol. 1968 Feb;50(2):129-37
4868034
Lancet. 2006 Feb 25;367(9511):668-78
16503465
Arthritis Rheum. 2000 Jul;43(7):1488-95
10902750
Inflamm Res. 2007 Apr;56(4):168-74
17522815
Arthritis Rheum. 2004 Oct;50(10):3286-95
15476228