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I G Colditz

Publications and source records attributed to I G Colditz.

61 records · Page 4Linked to original sources

Kinetics of neutrophil accumulation in acute inflammatory lesions induced by chemotaxins and chemotaxinigens.

The influx of neutrophils into cutaneous lesions induced with the chemotaxins formylmethionyl-leucyl-phenylalanine (FMLP), platelet-activating factor (PAF), and alpha-casein, and the chemotaxinigens endotoxin and zymosan peaked at 2 to 4 hr and then rapidly declined. In contrast, concanavalin A (Con A) induced a biphasic influx of neutrophils with an initial peak at 2 hr and a subsequent, prolonged peak between 6 and 10 hr. When the kinetics of the neutrophil influx into lesions induced with FMLP at 10(-5) M, 10(-6.5) M and 10(-8) M were examined, it was found that a comparable proportion of the total cell influx entered lesions induced with each concentration of FMLP at each time point. This result indicates that the kinetics of the neutrophil influx into an inflammatory lesion is not dependent on the concentration of chemotaxin within the lesion. The inflammatory potency of FMLP, PAF, alpha-casein, Con A, and endotoxin were compared with leukotriene B4 (LTB4) and zymosan-activated plasma (ZAP) as a source of C5 fragments. Equipotent concentrations were 10(-4) M alpha-casein, 10(-5) M PAF, 10(-5.5) M LTB4 and Con A, 10(-6) M FMLP, 10(-7) M ZAP, and 10(-11) M endotoxin.

Acute Disease↗

Properties of neutrophils recruited into inflammatory foci with homologous or heterologous antigen in immunized ewes.

Studies were undertaken to determine functional properties of neutrophils attracted into involuted mammary glands of Staphylococcus aureus--immunized ewes by soluble antigens prepared from S. aureus (homologous antigen) or from Bacillus cereus (heterologous antigen). The ewes were immunized with an S. aureus vaccine known to stimulate synthesis of cytophilic IgG2 antibody, and the inflammatory responses were elicited 4-8 weeks later by infusing homologous antigen into one gland and heterologous antigen into the other. Inflammatory cells were collected at 2, 4, and 8 h postinfusion. The magnitude of the cellular responses was similar in both glands with high proportions of viable neutrophils. There were no significant differences between neutrophil populations from each gland for proportions of cells bearing cytophilic immunoglobulin, although the proportions of cytophilic immunoglobulin-positive cells from both glands were lower in 2-h exudates than in 4-h or 8-h exudates. In invitro phagocytosis assays using 3H-labeled S. aureus and B. cereus no differences could be detected between the two populations of neutrophils in terms of phagocytic efficacy using a range of bacteria-neutrophil ratios and various opsonizing treatments.

Animals↗

Novel immunofluorescent technique for identification of ovine immunoglobulins and other potential opsonins binding to live Staphylococcus aureus.

A qualitative in vitro technique has been developed for identification of potential opsonins (immunoglobulins G1, G2, A, M; the third component of ovine complement C3, and fibronectin) of sheep origin, binding to cell walls of viable Staphylococcus aureus. The technique uses monospecific antisera to these ovine proteins. The antisera are conjugated to FITC-protein A such that the protein A-binding sites in the Fc region of the immunoglobulin molecules are occupied with FITC-protein A complexes and are prevented, therefore, from binding to protein A in the staphylococcal cell wall. The technique is highly specific and sensitive, and once conjugated monospecific antisera are prepared, many tests can be done in a short time. Staphylococcus aureus incubated in samples of milk whey showed variable binding of immunoglobulins G1, G2, and M; immunoglobulin A was bound from only one sample of milk whey, and the third component of ovine complement C3- and fibronectin binding were not detected. Most samples of blood serum and colostral whey produced binding of immunoglobulins G1, G2, A, and M, and the third component of ovine complement C3 to the Staphylococcus aureus cell surface; fibronectin binding was found in serum but not in colostral whey. Washings from involuted mammary glands invariably produced binding of all immunoglobulins but not of the third component of ovine complement C3 or fibronectin.

Animals↗

The role of humoral and cellular mediators in enhanced mammary inflammatory reactions to staphylococcal infection in systemically immunized ewes.

Prior systemic immunization with live Staphylococcus aureus vaccine enhances the early recruitment of neutrophils into nonlactating mammary glands infected with staphylococci. The study investigates the role of humoral and cellular mediators in this phenomenon. Intramammary infusion of bacteria suspended in immune sheep serum did not enhance the inflammatory response to infection in nonimmunized ewes despite the presence of complement in the infused serum. Infusion of complement activated by incubation with zymosan evoked a massive neutrophil influx into mammary secretions by 4 hr after infusion. Hemolytic complement activity was not detected in mammary secretions of immunized or nonimmunized ewes. These findings indicate that, despite the inflammatory effect of complement activation, humoral immune factors did not promote neutrophil migration into infected glands. Mammary glands of systemically immunized ewes stimulated 5 days previously with staphylococcal soluble antigens (SSA) supported larger neutrophil influxes during staphylococcal infection than contralateral glands stimulated with endotoxin 5 days prior to infection. Exudates of SSA-stimulated glands had significantly higher cell concentrations, prior to infection, than endotoxin-stimulated glands; however elevated cell concentrations in endotoxin-stimulated glands of nonimmune ewes did not support enhanced inflammatory responses. These findings suggest that qualitative but not quantitative characteristics of mammary leucocytes influence the inflammatory response to infection in systemically immunized ewes.

Animals↗

Effect of immunisation on the early influx of neutrophils during staphylococcal mastitis in ewes.

The neutrophil influx into mammary secretions was studied in unimmunised, and in systemically and locally immunised, lactating and non-lactating ewes experimentally infected with Staphylococcus aureus. Systemic immunisation was effected by subcutaneous injection of live bacteria or by intramuscular injection of killed bacteria in Freund's incomplete adjuvant. The initial inflammatory response to infection of the mammary glands of systemically immunised lactating ewes was at first comparable with that for unimmunised, lactating ewes. However by eight hours after challenge the leucocyte concentrations were lower in systemically immunised ewes. In non-lactating ewes immunised with live vaccine, higher leucocyte concentrations and higher proportions of neutrophils were recorded four hours after infection (hpi) than for unimmunised ewes or ewes immunised with killed vaccine. Prior local immunisation, by unilateral infusion of killed bacteria into mammary glands, enhanced the initial neutrophil influx in comparison to infection of unimmunised contralateral glands of non-lactating ewes by four hpi. For these animals the proportion of neutrophils in washings from immunised glands were significantly greater than for unimmunised glands four and six hpi. In two of three locally immunised lactating ewes there was a larger neutrophil influx into secretions of locally immunised glands than unimmunised glands six hpi. Neutrophils comprised more than 93 per cent of leucocytes from all infected glands by eight hpi. The results suggest that differences in the rate of influx of neutrophils into infected mammary glands of immunised and unimmunised ewes could be attributed to immunological enhancement of neutrophil recruitment or to limitation of toxic damage to tissues with consequently diminished neutrophil invasion.

Animals↗

Some relationships between age, immune responsiveness and resistance to parasites in ruminants.

In the Australian livestock industries, susceptibility to infectious diseases is generally greater in young than in mature ruminants. The increased susceptibility is manifest as respiratory and intestinal infections (viral and bacterial) of calves, as well as fleece rot, flystrike and, especially, gastrointestinal parasitic infestations of young sheep. Lower resistance to infectious disease in young ruminants appears to be due largely to immunological hyporesponsiveness, and is not simply a consequence of their not having been exposed sufficiently to pathogens to develop active immunity. Young sheep have significantly lower proportions of CD4+ and CD8+ lymphocytes, but similar proportions of T19+ and B lymphocytes in blood, lymph and skin compared with mature sheep. Blood lymphocytes from young sheep produce less interferon-gamma in culture and young sheep invariably mount smaller antibody responses than do mature animals. Taken together, these findings begin to explain why young ruminants are more susceptible to infectious diseases in general, and to gastrointestinal parasites in particular, when compared to mature animals. Haematological markers of disease resistance, the prevalence of non-selected diseases and immune responses to vaccination were examined in the internal parasite-resistance flocks in Armidale NSW and the fleece rot/flystrike selection flocks at Trangie NSW. Any programme that seeks to improve resistance to parasitic or any other disease should have the capacity to make contemporary measurements of resistance to other diseases which are important in, or threaten, the production system.

Aging↗

Accumulation of leucocytes and cytokines in the lactating ovine udder during mastitis due to Staphylococcus aureus and Escherichia coli.

The accumulation of leucocytes in milk and in teat cistern tissues, and the presence of the cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in milk was studied during inflammation in the lactating ovine udder induced by Staphylococcus aureus and Escherichia coli. Milk and/or teat tissue samples were taken before and four, eight and 24 hours after inoculation. Both S aureus and E coli induced a significant accumulation of leucocytes in milk, S aureus from eight hours with a peak after 24 hours, and E coli from four hours, with a peak after eight hours. After the inoculation of S aureus the numbers of subepithelial neutrophils in the teat cistern tissues were increased after four hours and had increased further by eight hours. After the inoculation of E coli, tissue neutrophil numbers peaked at four hours and were still high at eight hours. Large numbers of S aureus were recovered from milk throughout the experiments whereas the recovery of E coli diminished over time. TNF-alpha, IL-8 and IL-1 beta were detected in milk during the inflammation, and low levels of GM-CSF and IFN-gamma were also observed occasionally. Of the cytokines measured, TNF-alpha and IL-8 reached the highest concentrations, accumulating in a similar pattern to the leucocytes for both infections. IL-1 beta was detected mainly during S aureus-induced inflammation, indicating differences in the inflammatory responses elicited by the organisms.

Animals↗