Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and progression of acute allograft rejection.

The identification of early inflammatory events after transplant in solid tissue organ grafts that may direct T cell recruitment and promote acute allograft rejection remain largely unknown. To better understand temporal aspects of early inflammatory events in vascularized organ grafts, we tested the intragraft expression of four different chemokines in heterotopically transplanted A/J (H-2(a)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipient mice from 1.5 to 48 h after transplant. Similar temporal expression patterns and equivalent levels of chemokine expression were observed in both syngeneic and allogeneic cardiac allografts during this time period. Expression of the neutrophil chemoattractant growth-related oncogene alpha (KC) was observed first and reached peak levels by 6 h after transplant and was followed by the monocyte/macrophage chemoattractant protein-1 (JE) and then macrophage inflammatory proteins 1beta and 1alpha. Administration of rabbit KC antiserum to allograft recipients within 30 min of cardiac transplantation attenuated downstream events including intra-allograft expression of the T cell chemoattractants IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, cellular infiltration into the allograft, and graft rejection. Similarly, depletion of recipient neutrophils at the time of transplantation significantly extended allograft survival from day 8 to 10 in control-treated recipients up to day 21 after transplant. These results indicate the induction of highly organized cascades of neutrophil and macrophage chemoattractants in cardiac grafts and support the proposal that early inflammatory events are required for optimal recruitment of T cells into allografts during the progression of acute rejection of cardiac allografts.

Long-term continence and patient satisfaction after artificial sphincter implantation for urinary incontinence after prostatectomy.

PURPOSE: We assess long-term continence and patient satisfaction after implantation of the AMS Sphincter 800 (American Medical Systems, Minnetonka, Minnesota) in men who were incontinent after total and subtotal prostatectomy. MATERIALS AND METHODS: Patients who had an artificial urinary sphincter implanted for urinary incontinence after prostatectomy and a minimum of 20 months of followup were identified from a patient database. The medical records of these 209 patients were reviewed, and a questionnaire was mailed. Telephone contact was attempted with patients who did not respond to the questionnaire. Of the 209 patients 11 (5%) had undergone device removal, 34 (16%) were deceased and an additional 51 (24%) could not be contacted for followup. Our study group consisted of the 113 patients with artificial urinary sphincters who could be contacted for followup. Mean followup was 73 months (range 20 to 170). RESULTS: There were 4 (4%) patients who were dry and continent and 68 (60%) were incontinent using 0 to 1 pad daily. An additional 35 (31%) patients required 2 to 3 pads daily and 5 (4%) used more than 3 daily. There were 14 (12%) patients who had undergone surgical revision of the device. Of the 113 patients 31 (28%) were very satisfied, 50 (45%) satisfied, 20 (18%) neutral, 7 (6%) dissatisfied and 4 (4%) very dissatisfied. One patient was not using his device to control continence. CONCLUSIONS: Artificial urinary sphincter implantation offers men who are incontinent after prostatectomy a reasonable chance for obtaining long-term satisfactory urinary control, although complete continence is unusual.

Intraallograft chemokine RNA and protein during rejection of MHC-matched/multiple minor histocompatibility-disparate skin grafts.

Chemokines direct leukocyte recruitment into sites of tissue inflammation and may facilitate recruitment of leukocytes into allografts following transplantation. Although the expression of chemokines during rejection of MHC-disparate allografts has been examined, chemokine expression in MHC-matched/multiple minor histocompatibility Ag-disparate allografts has not been tested. The intraallograft RNA expression of several C-X-C and C-C chemokines was tested during rejection of full thickness skin grafts from B10. D2 donors on control Ig-, anti-CD4 mAb-, and anti-CD8 mAb-treated BALB/c recipients. In all recipients, two patterns of intragraft chemokine expression were observed during rejection of these grafts: 1) macrophage-inflammatory protein-1alpha, macrophage-inflammatory protein-1beta, GRO-alpha (KC), JE, and IFN-gamma-inducible protein (IP-10) were expressed at equivalent levels in allo- and isografts for 2-4 days posttransplant and then returned to low or undetectable levels; and 2) IP-10 and monokine induced by IFN-gamma (Mig) were expressed in the allografts 3 days before rejection was completed, suggesting a possible role in recruiting primed T cells into the allograft. Three days before completion of rejection, intraallograft IP-10 protein was restricted to the epidermis, whereas Mig was located in the lower dermis and associated with the intense infiltration of mononuclear cells. Treatment of B10.D2 recipients with rabbit antiserum to Mig, but not to IP-10, delayed rejection of the allografts 3-4 days. The results suggest that Mig mediates optimal recruitment of T cells into MHC-matched/multiple minor histocompatibility Ag-disparate allografts during rejection.