Biomedical subjects

A L Nieves

Publications and source records attributed to A L Nieves.

24 records · Page 2Linked to original sources

PubMed1986

Leukotrienes cause eosinophil emigration into conjunctival tissue.

The ability of LTB4, LTC4, the 5S,6R and 5R,6S LTD4 stereoisomers, and LTE4 to evoke leukocyte infiltration into the conjunctiva was demonstrated in the guinea pig by histological and light microscopy techniques. LTD4 and LTE4 demonstrated a dose-dependent and predominantly eosinophilic infiltrate over the selected dose range (10 ng to 1000 ng), while there was only a minimal response to LTC4. LTB4 produced marked eosinophil infiltrates only at the highest dose; scattered neutrophil infiltrates were also noted at the high dose of LTB4. The 5R,6S LTD4 stereoisomer did not evoke any leukocyte infiltration. The SRS-A antagonist, FPL 55712, abolished peptidoleukotriene-induced eosinophil emigration, and indomethacin pre-treatment had no inhibitory effect, indicating direct mediation of this response by LTs. Histamine caused a comparable eosinophilia over a dose range of 10 micrograms to 1000 micrograms. LT-induced eosinophil emigration was directed to the conjunctival epithelium; the cells appeared intact and no tissue damage was observed. These results may have relevance in the areas of allergic conjunctivitis and asthma research.

Animals↗

PubMed1986

Conjunctival eosinophil infiltration evoked by histamine and immediate hypersensitivity. Modification by H1- and H2-receptor blockade.

The present histological studies have demonstrated that histamine causes dose-dependent eosinophil infiltration into the conjunctiva. A highly directional movement toward the conjunctival epithelium was observed, and the presence of large numbers of degranulating eosinophils appeared to result in epithelial cell damage and goblet cell discharge. Blockade of H2-receptors by systemic cimetidine pretreatment significantly inhibited the eosinophil infiltration elicited by an intermediate histamine dose, whereas the H1-receptor blockade produced by systemic pyrilamine pretreatment markedly reduced the response to all histamine doses. The pyrilamine-insensitive residual eosinophil infiltrate was not affected by administering a cimetidine-pyrilamine combination. In animals presensitized to ovalbumin, antigen challenge evoked extensive and directional emigration of eosinophils toward the conjunctival epithelium with resultant exfoliation and depletion of goblet cell populations. In conjunctival immediate hypersensitivity, neither cimetidine nor pyrilamine alone produced an inhibitory effect, but a cimetidine-pyrilamine combination caused a significant reduction in the number of infiltrating eosinophils and prevented epithelial damage and goblet cell depletion. These results suggest that histamine may participate in the recruitment of eosinophils during immediate hypersensitivity reactions. The differential effect of pyrilamine on the eosinophil infiltration evoked by histamine or immediate hypersensitivity may, perhaps, reflect the importance of increased microvascular permeability in facilitating eosinophil emigration.

Animals↗

PubMed1986

Conjunctival immediate hypersensitivity: re-evaluation of histamine involvement in the vasopermeability response.

The recent development of a technique for quantitative measurement of conjunctival microvascular permeability has permitted detailed pharmacological evaluation of H1- and H2-receptor involvement in histamine-induced increases in conjunctival microvascular permeability and the role of histamine in microvascular permeability changes associated with immediate hypersensitivity responses in the conjunctiva. The conjunctival microvascular permeability response to histamine appears to be entirely mediated by H1-receptors. Pyrilamine (H1-receptor antagonist) virtually abolished the increase in conjunctival extravascular albumin content produced by graded doses of histamine, whereas cimetidine (H2-receptor antagonist) was ineffective. Moreover, selective histamine H2-receptor agonists did not elicit a dose-dependent vasopermeability response in the conjunctiva. Although H1-receptor blockade essentially abolished the microvascular permeability response to histamine, it only partially attenuated the conjunctival microvascular permeability response associated with immediate hypersensitivity and compound 48-80. It appears that conjunctival inflammation caused by mast cell degranulation comprises both a histaminergic and a nonhistaminergic component.

Albumins↗

PubMed1985

Histamine H1- and H2-receptor involvement in eosinophil infiltration and the microvascular changes associated with cutaneous anaphylaxis.

Several substances alter eosinophil motility, but the relative importance of these putative mediators in immediate hypersensitivity remains unclear. The present study has re-investigated the role of histamine in type I allergic eosinophil infiltration, and the temporally associated microvascular events, by examining the effect of H1- and H2-receptor antagonist pretreatment. A combination of cimetidine and pyrilamine significantly reduced eosinophil accumulation, whereas neither antagonist alone was effective. Similarly, cutaneous hyperemia, measured indirectly as ear surface temperature, was reduced only by the cimetidine-pyrilamine combination. Pyrilamine partially attenuated the increase in microvascular permeability, but the addition of cimetidine provided no further reduction. It appears that histamine participates significantly in mediating both the microvascular changes and the eosinophil infiltration evoked by cutaneous anaphylaxis. The histaminergic component of increased microvascular permeability appears to be an H1-receptor mediated phenomenon. However, blockade of both H1- and H2-receptor subtypes is required to inhibit the hyperemia and eosinophil infiltration responses.

Animals↗

PubMed1985

Topical anti-inflammatory activity of beta 2-adrenoceptor agonists in the conjunctiva.

Increased microvascular permeability is believed to involve the contraction of venular endothelial cells, which results in the formation of leaking gaps in the postcapillary segment of the microvasculature. Several reports have suggested that interendothelial cell gap formation caused by permeability factors may be functionally antagonized by locally administered beta 2-adrenoceptor agonists. This represents a potentially novel approach for reducing inflammatory episodes in a variety of externally accessible tissues. The studies described herein extend these findings to the conjunctiva, where the relatively selective beta 2-adrenoceptor agonists salbutamol and terbutaline reduced the microvascular permeability response to histamine. Similarly, pretreatment with salbutamol or terbutaline inhibited the increase in conjunctival microvascular permeability associated with experimental immediate hypersensitivity, which indicates potential utility for allergic conjunctivitis.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Time-dependent differences in the vasopermeability response to intradermal peptidoleukotrienes.

The time course of extravascular albumin accumulation responses elicited by the leukotrienes LTC4, LTD4, LTE4, and histamine in the skin were compared in the conscious guinea pig. During the initial 15-min period, comparison of the dose-response curves revealed that histamine produced a much larger increase in extravascular albumin content than any of the leukotrienes. One hour after intradermal injection and at subsequent time intervals, the response to LTD4 had increased in magnitude so that it equaled the response produced by histamine. This was apparent from comparison of the time courses of extravascular albumin accumulation for intermediate doses of LTD4 and histamine and also from comparison of dose-response relationships at 4 h post intradermal injection. In contrast to LTD4, the magnitude of the microvascular permeability responses to LTC4 and LTE4 remained relatively small even over an extended time scale. Although histamine produced a large initial response, this also remained essentially unchanged over a 4-h period. It appears that LTD4 may produce a unique, time-dependent cutaneous microvascular permeability response and measurements over 15-30-min periods may underestimate its activity as a vasopermeability factor. The time-dependent effects of LTD4 on albumin extravasation cannot be ascribed to leukocyte infiltration into the skin since LTC4, LTD4, and LTE4 were entirely without effect in this regard.

Albumins↗