A comparison of allergen and polycation induced cutaneous responses in the rabbit

Abstract

1 Allergic in¯ammatory responses contribute to the symptoms of a number of diseases including atopic dermatitis, asthma and rhinitis. Cationic proteins are released from in¯ammatory cells and levels are known to be raised in disease states. 2 Using an in vivo model of acute in¯ammation, we investigated the characteristics of cutaneous responses to antigen (Alternaria tenuis, AT) and poly-L-lysine (PLL, used as a paradigm for cationic proteins). We aimed to compare the in¯ammatory pro®le of cationic polypeptides and the allergic response and to identify similarities and dierences between these responses. 3 Responses to intradermal injection of the polycation, PLL and antigen were compared using radiolabelled protein ( 125 I-bovine serum albumin, BSA) and cells ( 111 In-neutrophils, PMN) to study plasma exudation (PE) and PMN accumulation (PMNA) in the skin of AT sensitized rabbits. 4 Both PLL and antigen caused dose-related increases in PE and PMNA. PE (and PMNA) responses to PLL were prolonged (up to 3 h), as were those to antigen. This is in contrast to PE responses to fMLP which were maximal at 45 min. 5 In immunized animals, treated with colchicine (1 mg kg 71 i.v.), PE responses to the directly acting mediator, bradykinin (BK), were not aected, whereas PE responses to the neutrophil dependent mediator, f-met-leu-phe (fMLP), were signi®cantly (P50.01) reduced. Antigen-induced PE responses were signi®cantly (50, 500 (P50.05); 200 (P50.01) p.n.u. site 71 ) inhibited by colchicine, but PLL-induced responses were not signi®cantly aected. 6 We conclude that although PLL-induced responses had a similar time course to those of antigen, some dierences were observed between responses, which indicate that although polycations may contribute to allergic responses, these two responses are produced by distinct mechanisms.

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

“…Furthermore, in asthma, increased arginase activity diverts L-arginine toward increased production of the polycations spermine, spermidine, and putrescine (4, 5, 11). Although in human peripheral blood monocytes spermine exhibits anti-inflammatory properties (12), associations between increases in polycations in the asthmatic airway mucosa and AHR/airway remodeling and inflammation (4, 5, 13) have long been apparent and ascribed to their positive charge (9). However, the cause-effect relationship remains hitherto unexplained.…”

The effects of heparin and related molecules on vascular permeability and neutrophil accumulation in rabbit skin

“…We have previously shown that i.d. injection of PLL causes a dose and time dependent PE and PMNA response and that the PE response is PMN independent in the rabbit (Jones et al ., 2001). Ten minute i.d.…”

“…The leukocyte pellets were combined and resuspended in 2 ml platelet poor plasma (PPP), and 10 μl taken for counting. The cell preparation was >95% neutrophils of which >95% were viable (Jones et al ., 2001). Cells were incubated at room temperature with mercaptopyridine (5 min) followed by 111 In Cl 3 (11.1 MBq, 30 min).…”

“…site −1 , and PLL, at 100 μg site −1 . These doses were determined from earlier dose response experiments (Jones et al ., 2001). Although earlier experiments showed that it was not necessary to mix PLL with PGE 2 to obtain adequate PE and PMNA responses (Jones et al ., 2001), in the present study PLL was, in some instances, mixed with PGE 2 , and these are specified in the text and Figure legends.…”

“…These doses were determined from earlier dose response experiments (Jones et al ., 2001). Although earlier experiments showed that it was not necessary to mix PLL with PGE 2 to obtain adequate PE and PMNA responses (Jones et al ., 2001), in the present study PLL was, in some instances, mixed with PGE 2 , and these are specified in the text and Figure legends. This was performed in order to rule out the possibility that the inhibitory effect of UH on PLL (an effect which was not observed on fMLP‐ or LTB 4 ‐induced responses) might have been due to the fact that PLL was the only stimulus not to be mixed with PGE 2 .…”